Zheng Natalie N, McElrath M Juliana, Sow Papa-Salif, Hawes Stephen E, Diallo-Agne Habibatou, Stern Joshua E, Li Fusheng, Mesher Andrew L, Robinson Akeliah D, Gottlieb Geoffrey S, Huang Yunda, Kiviat Nancy B
Department of Pathology, University of Washington, Seattle, WA 98195, USA.
J Virol. 2007 Sep;81(17):9061-71. doi: 10.1128/JVI.00117-07. Epub 2007 Jun 20.
Progressive immune dysfunction and AIDS develop in most cases of human immunodeficiency virus type 1 (HIV-1) infection but in only 25 to 30% of persons with HIV-2 infection. However, the natural history and immunologic responses of individuals with dual HIV-1 and HIV-2 infection are largely undefined. Based on our previous findings, we hypothesized that among patients with dual infection the control of HIV-1 is associated with the ability to respond to HIV-2 Gag epitopes and to maintain HIV-specific CD4(+) T-cell responses. To test this, we compared the HIV-specific ex vivo IFN-gamma enzyme-linked immunospot (ELISPOT) assay responses of 19 dually infected individuals to those of persons infected with HIV-1 or HIV-2 only. Further, we assessed the functional profile of HIV Gag-specific CD4(+) and CD8(+) T cells from nine HIV dually infected patients by using a multicolor intracellular cytokine staining assay. As determined by ELISPOT assay, the magnitude and frequency of IFN-gamma-secreting T-cell responses to gene products of HIV-1 were higher than those to gene products of HIV-2 (2.64 versus 1.53 log(10) IFN-gamma spot-forming cells/10(6) cells [90% versus 63%, respectively].) Further, HIV-1 Env-, Gag-, and Nef- and HIV-2 Gag-specific responses were common; HIV-2 Nef-specific responses were rare. HIV-specific CD4(+) T helper responses were detected in nine of nine dually infected subjects, with the majority of these T cells producing gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and, to a lesser extent, interleukin-2. The HIV-1 plasma viral load was inversely correlated with HIV-2 Gag-specific IFN-gamma-/TNF-alpha-secreting CD4(+) and HIV-2 Gag-specific IFN-gamma-secreting CD8(+) T cells. In conclusion, the T-cell memory responses associated with containment of single HIV-1 and HIV-2 infection play a similar significant role in the immune control of dual HIV-1 and HIV-2 infection.
在大多数人类免疫缺陷病毒1型（HIV-1）感染病例中会出现进行性免疫功能障碍和艾滋病，但在HIV-2感染患者中只有25%至30%会出现这种情况。然而，同时感染HIV-1和HIV-2的个体的自然病史和免疫反应在很大程度上尚不清楚。基于我们之前的研究结果，我们推测在双重感染患者中，HIV-1的控制与对HIV-2 Gag表位作出反应并维持HIV特异性CD4(+) T细胞反应的能力有关。为了验证这一点，我们比较了19名双重感染个体与仅感染HIV-1或HIV-2个体的HIV特异性体外干扰素-γ酶联免疫斑点（ELISPOT）检测反应。此外，我们通过使用多色细胞内细胞因子染色检测法评估了9名HIV双重感染患者的HIV Gag特异性CD4(+)和CD8(+) T细胞的功能特征。通过ELISPOT检测确定，对HIV-1基因产物分泌干扰素-γ的T细胞反应的强度和频率高于对HIV-2基因产物的反应（分别为2.64对1.53 log(10)干扰素-γ斑点形成细胞/10(6)个细胞[分别为90%对63%]）。此外，HIV-1 Env、Gag和Nef以及HIV-2 Gag特异性反应很常见；HIV-2 Nef特异性反应很少见。在9名双重感染受试者中有9名检测到了HIV特异性CD4(+) T辅助反应，这些T细胞大多数产生γ干扰素（IFN-γ）和肿瘤坏死因子α（TNF-α），在较小程度上产生白细胞介素-2。HIV-1血浆病毒载量与HIV-2 Gag特异性IFN-γ/TNF-α分泌性CD4(+)以及HIV-2 Gag特异性IFN-γ分泌性CD8(+) T细胞呈负相关。总之，与单一HIV-1和HIV-2感染控制相关的T细胞记忆反应在双重HIV-1和HIV-2感染的免疫控制中发挥着类似的重要作用。
